CHD8: Chromodomain Helicase DNA Binding Protein 8
A key regulator of chromatin remodeling and neurodevelopment, frequently mutated in autism spectrum disorder
Gene Information Card
| Symbol | CHD8 |
|---|---|
| Full Name | Chromodomain Helicase DNA Binding Protein 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 57680 ncbi.nlm.nih.gov/gene/57680 |
| Ensembl ID | ENSG00000100888 |
| UniProt ID | Q9HCK8 |
| OMIM ID | 610528 |
| HGNC ID | 20153 |
| Aliases | HELSNF1, FLJ20397, KIAA1564 |
Description
CHD8 encodes a member of the chromodomain helicase DNA-binding protein family that functions as an ATP-dependent chromatin remodeler. It regulates gene expression by altering chromatin structure, particularly through interaction with beta-catenin and repression of Wnt signaling. CHD8 is essential for neurodevelopment and is one of the most frequently mutated genes in autism spectrum disorder (ASD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism spectrum disorder (ASD) | Loss-of-function mutations disrupt chromatin remodeling and Wnt signaling, leading to altered neuronal gene expression | ClinVar, OMIM |
| Intellectual disability | De novo truncating mutations impair neurodevelopmental gene regulation | ClinVar, OMIM |
| Schizophrenia | Rare missense variants may contribute to synaptic dysfunction | ClinVar |
| Macrocephaly | CHD8 haploinsufficiency leads to increased brain growth via dysregulated beta-catenin | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 18.5 | Medium |
| Brain (cerebellum) | 15.2 | Medium |
| Testis | 12.8 | Medium |
| Thyroid | 10.1 | Low |
| Heart | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 22.1 | Neuronal model |
| HEK293 (embryonic kidney) | 19.4 | High expression |
| HeLa (cervical carcinoma) | 15.6 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 12.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4666C>T (p.Arg1556*) | Nonsense | De novo | Loss of function; truncates protein, associated with ASD |
| c.2620G>A (p.Glu874Lys) | Missense | Rare | Alters helicase domain, reduced chromatin remodeling activity |
| c.1210_1211del (p.Leu404fs) | Frameshift | De novo | Loss of function; linked to macrocephaly and ASD |
| c.5113G>A (p.Gly1705Arg) | Missense | Rare | Dominant negative effect on beta-catenin regulation |
Mutation functional classification
Loss of Function (LOF)
Most common mechanism; nonsense, frameshift, and splice-site mutations lead to haploinsufficiency, disrupting chromatin remodeling and Wnt signaling, strongly associated with ASD and macrocephaly.
Gain of Function (GOF)
Not well documented; no clear gain-of-function mutations reported in CHD8.
Dominant Negative (DN)
Rare missense mutations (e.g., p.Gly1705Arg) may interfere with wild-type CHD8 function, altering beta-catenin interaction and gene expression.
View complete mutation data：
Gene Ontology (GO)
| • ATP-dependent chromatin remodeling (GO:0043044) | • DNA binding (GO:0003677) |
| • Helicase activity (GO:0004386) | • Regulation of transcription by RNA polymerase II (GO:0006357) |
| • Negative regulation of Wnt signaling pathway (GO:0030178) | • Chromatin organization (GO:0006325) |
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• Chromatin remodeling by CHD8 (Reactome: R-HSA-9018519)
• Transcriptional regulation by beta-catenin (Reactome: R-HSA-201681)
Protein Summary
CHD8 is a 280 kDa ATP-dependent chromatin remodeler containing two chromodomains, a helicase/ATPase domain, and a DNA-binding domain. It binds to methylated histones and ATP to remodel nucleosomes, regulating gene expression. CHD8 interacts with beta-catenin to repress Wnt target genes, crucial for neural progenitor proliferation and differentiation. Mutations cause chromatin dysregulation, leading to neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHD8 Knockout HEK293 Cell Line | EDJ-KQ287 | Human | 57680 | Details Get a Quote |
| CHD8 Knockout HeLa Cell Line | EDJ-KQ17956 | Human | 57680 | Details Get a Quote |
| CHD8 Knockout A-549 Cell Line | EDJ-KQ18398 | Human | 57680 | Details Get a Quote |
| CHD8 Knockout HCT 116 Cell Line | EDJ-KQ18399 | Human | 57680 | Details Get a Quote |
